Fish oil and B vitamins had no apparent effect on cancer risk in patients with a history of cardiovascular disease, data from a randomized trial showed.

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Note that in this study in patients with prior cardiovascular disease, five years of supplementation with B vitamins and/or omega-3 fatty acids had no beneficial effects on cancer outcomes.

Note that supplementation had no effect on cancer risk in men, but women treated with omega-3 fatty acids had a threefold higher cancer incidence and a five-fold higher cancer mortality.

Fish oil and B vitamins had no apparent effect on cancer risk in patients with a history of cardiovascular disease, data from a randomized trial showed.

Whether patients received the vitamins and fish oil alone or in combination, they had a nonsignificant 15% to 17% higher risk of cancer and cancer-related death.

Subgroup analysis revealed significant interaction between treatment and sex. Supplementation had no effect on cancer risk in men (who accounted for more than 80% of the cancers) but women treated with omega-3 fatty acids had a threefold higher cancer incidence and a five-fold higher cancer mortality.

"This study does not support dietary use of B vitamins or omega-3 fatty acids for cancer prevention," Valentina A. Andreeva, PhD, of the University of Paris, and co-authors wrote in an article published online in Archives of Internal Medicine.

"The preliminary evidence of adverse effects among women necessitates confirmation before firm conclusions could be drawn."

The results added to equivocal evidence from prior randomized clinical trials of supplements for cancer prevention, including trials of patients with heart disease.

A Norwegian study showed an increased cancer risk in patients with ischemic heart disease treated with folic acid and vitamin B12 as compared with vitamin B6 or placebo (JAMA 2009; 302: 2119-2126). However, a meta-analysis of randomized trials found no effect of folic acid supplementation on cancer risk in patients at increased risk of cardiovascular disease (Arch Intern Med 2010; 170: 1622-1631).

Trials of omega-3 fatty acids have generally focused on cancer treatment rather than chemoprevention, the authors wrote. Evidence from epidemiologic studies has been mixed.

The paucity and inconclusiveness of relevant data prompted the authors to perform a secondary analysis of the Supplementation with Folate, Vitamins B6 and B12 and/or Omega-3 Fatty Acids (SU.FOL.OM3) trial.

The primary objective of SU.FOL.OM3 was to examine the effect of supplementation on secondary prevention of cardiovascular disease events, including mortality. The results showed no effect of supplements on the main outcome (BMJ 2010; DOI:10.1136/bmj.c6273).

The trial included 2,501 patients ages 45 to 80 who were randomized to one of four treatment groups: vitamins B6 and B12; omega-3 fatty acids; B vitamins and omega-3 fatty acids; or placebo. Treatment continued for five years.

The outcomes of interest were cancer incidence and cancer mortality.

The study population comprised 514 women and 1,987 men. After excluding nonmelanoma skin cancer, the investigators found that 174 study participants (7%) developed cancer during the follow-up period. Men had 145 of the cancers and women 29, resulting in incidences of 7.3% and 5.6%, respectively.

The most common sites of cancer in men were prostate (50), lung/bronchus (22), bladder (16), and colorectal (13). Nine women developed breast cancer, four had lung cancer, and three had colorectal cancer.

Cancer mortality was 2.3% for the entire study population, including 2.4% in men and 2.1% in women.

Separate analyses by treatment assignment showed that patients treated with B vitamins had a nonsignificant hazard ratio of 1.15 for cancer incidence and 1.17 for cancer mortality as compared with the placebo group. Analysis by sex also showed no significant effect of B vitamins on cancer outcomes in men or women.

After adjustment for age, homocysteine and creatinine concentrations, and prior unstable angina, women had a twofold increased risk of cancer, although the difference did not achieve significance (P=0.06).

In the overall analysis, omega-3 fatty acids did not significantly affect cancer incidence (HR 1.17) or cancer mortality (HR 1.47) as compared with the placebo group.

Analysis for interaction by sex showed no significant effects in men. However, women had a statistically significant hazard ratio of 3.02 for cancer incidence and 5.49 for cancer mortality, both of which were significant as compared with the placebo arm.

The study was supported by the French National Research Agency, the French Ministry of Health, Sodexo, Candia, Unilever, Danone, Roche Laboratories, Merck Eprova AG, and Pierre Fabre Laboratories.

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